Cancer chemotherapy 1 Flashcards
what is the difference between combination therapy vs single agent
Originally single chemotherapeutic agents used to treat cancer until the early 1960’s.
Combination therapy coupled with more aggressive treatment regimen became popular in 1960’s.
Combination therapy led to increased remission, in terms of both patient numbers and length of remission time
More aggressive regimen results in increased side effects
New targeted treatment options such as tyrosine kinase inhibitor and mono-clonal antibodies reignite competition over combination or single agent therapy.
what are chemotherapy targets?
Nucleic Acids
- Multiple ways to target Nucleic Acids
–>DNA double helix
–>DNA synthesis
–> Synthesis of DNA building blocks
Protein Targets
-Inhibition of enzymes or receptors
-Interaction with structural proteins
Other Biomolecules
-Cell surface features
what are the classification of drugs?
Alkylating drugs: damage DNA and hence interfere with cell replication. e.g. Cyclophosphamide, Ifosfamide, chlorambucil, melphalan, busulfan, lomustine, carmustine, estramustine, treosulfan, thiotepa, mitobronitol, dacarbazine and temozolomide, platinum compounds, procarbazine.
Cytotoxic antibiotics: interact with DNA and proteins e.g. doxorubicin, epirubicin, idarubicin, daunorubicin, mitoxantrone, bleomycin, dactinomycin, mitomycin, etoposide.
Antimetabolites: incorporated into new nuclear material or combine irreversibly with vital cellular enzymes preventing normal cellular division. e.g. methotrexate, capecitabine, cytarabine, fludarabine, cladribine, gemcitabine, fluorouracil, pemetrexed, raltitrexed, mercaptopurine, tegafur.
Sex hormones and hormone antagonists: Target biological hormonal pathways and interact with receptor binding sites. Include oestrogens, progestogens, hormone antagonists e.g. diethylstilbestrol, ethinylestradiol, medroxyprogesterone, megestrol, tamoxifen, anastrazole, letrozole.
Drugs affecting the immune response: Include antiproliferative immunosuppressants and immunomodulating drugs. e.g. thalidomide (not licensed), interferon alfa, aldesleukin
Vinca alkaloids : e.g. vinblastine, vincristine, vindesine, vinorelbine,
Other: e.g., taxanes
what is the role of alkylating drugs?
examples?
Alkylating drugs: damage DNA and hence interfere with cell replication. e.g. Cyclophosphamide, Ifosfamide, chlorambucil, melphalan, busulfan, lomustine, carmustine, estramustine, treosulfan, thiotepa, mitobronitol, dacarbazine and temozolomide, platinum compounds, procarbazine.
what is the role of cytotoxic antibiotic
examples
Cytotoxic antibiotics: interact with DNA and proteins e.g. doxorubicin, epirubicin, idarubicin, daunorubicin, mitoxantrone, bleomycin, dactinomycin, mitomycin, etoposide.
what is the role of antimetabolites
examples
Antimetabolites: incorporated into new nuclear material or combine irreversibly with vital cellular enzymes preventing normal cellular division. e.g. methotrexate, capecitabine, cytarabine, fludarabine, cladribine, gemcitabine, fluorouracil, pemetrexed, raltitrexed, mercaptopurine, tegafur.
what is the role of sex hormones and hormone antagonists
Sex hormones and hormone antagonists: Target biological hormonal pathways and interact with receptor binding sites. Include oestrogens, progestogens, hormone antagonists e.g. diethylstilbestrol, ethinylestradiol, medroxyprogesterone, megestrol, tamoxifen, anastrazole, letrozole.
what is the roles of drugs that affect the immune response
Drugs affecting the immune response: Include antiproliferative immunosuppressants and immunomodulating drugs. e.g. thalidomide (not licensed), interferon alfa, aldesleukin
what are alkylating agent
-cross linking
Alkylating agents are highly electrophilic compounds that react with nucleophiles to form strong covalent bonds.( lone pair is not involved in the aromatic ring which makes them nucleophilic - n7 ) There are several nucleophilic groups in DNA such as N-1 and N-3 of adenine bases, N-3 of cytosine and in particular N-7 of guanine.
Alkylating agents include nitrogen mustards, nitrosoureas, cisplatin and analogues, dacarbazine and procarbazine and mitomycin C. They are used to treat a wide range of cancers including leukaemia, non-hodgkin lymphoma, Hodgkin disease, multiple myeloma, lung, breast, testicular and ovarian cancers.
Thus drugs with two alkylating groups can react with guanine on each chain and cross-link the strands such that they disrupt replication or transcription
Alternatively the drug can link two guanine groups on the same chain such that the drug is attached like a limpet to the side of the DNA helix. That portion of DNA becomes masked and the necessary enzymes required for DNA function cannot gain access.
what is chlromethine
too reactive to survive in oral admin
given in iv - treatment of Hodgkin lymphoma via multidrug regime
what is melphalan
less reactive alkaylating agent
mimic phenyl alaline
can be given orally
used to treat multiple myeloma, ovarian and breast cancers
what is cyclophosphamide
broad application
prodrug
not toxic itself but metabolised in the liver by cytochrome P540 to the active agent
can be taken orally without any damage to the gut wall
what is cisplatin?
Chlorine is nex to each other
